Drug therapy of advanced Parkinson's disease is unsatisfactory. Patients suffer from motor fluctuations ranging from severe akinetic "off" periods to episodes of uncontrolled abnormal movements. Replacing destroyed dopamine cells and nerve terminals with transplants of embryonic mesencephalon may restore regulated release of dopamine and provide more normal motor control. Open clinical trials of transplants of human embryonic dopamine cells at the University of Colorado and other centers have shown that stereotactic implants into the putamen of patients with advanced Parkinson's Disease (Hoehn and Yahr Stages 3 and 4) appear to produce amelioration of many aspects of Parkinson's disease. Freezing spells, dyskinetic episodes, and akinesia have been moderated, speech and walking have improved, and doses of L-dopa have been reduced up to 50%. To prove that the observations of these open trials are valid, a controlled study is now required. By combining the expertise of a major Parkinson clinical research center at Columbia-Presbyterian Hospital in New York with the experience of fetal neural transplantation at the University of Colorado, we will perform a placebo controlled, double blind study of embryonic implants into patients with intractable Parkinson's disease. Patients will be stratified by age. Using intensive clinical evaluation in the Clinical Research Center at Columbia and a novel home based computer and video taping system, patients will be monitored for at least 3 months prior to surgery and for a minimum of one year after surgery. Pre and postoperative 18-fluorodopa PET scans will be performed to document the severity of striatal dopamine depletion before surgery and to follow the development of transplants after surgery. At the University of Colorado, patients will be randomly assigned to receive embryonic tissue implants or sham surgery with craniotomy alone. Patients and their neurologists at Columbia- Presbyterian will be unaware of the surgical procedure performed. Tissue from 7 to 8 week post conception embryos will be used. Embryonic tissue will be matched for ABO blood group compatibility with the patient. Using CT guided stereotactic techniques, tissue will be injected bilaterally into putamen with up to 16 needle passes during a single operation. Control patients will be offered transplant with embryonic tissue one year after their initial sham surgery. If successful, these controlled experiments will prove that fetal mesencephalic dopamine cell implants offer significant reversal of severe Parkinson's disease and will establish whether patient age influences transplant success.